Journal
STEM CELLS INTERNATIONAL
Volume 2020, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2020/2685820
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Funding
- Shanghai Pujiang Program [2016PJD032]
- Ministry of Education Research Fund for Returned Personnel Research [20050054]
- National Natural Science Foundation of China [31300811]
- Clinical Research of the Ninth People's Hospital, Shanghai Jiaotong University [JYLJ201811]
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Purpose. Recent evidence has shown that CD4(+) T helper (Th) cells are involved in renal inflammation and fibrosis. However, whether renal fibrosis can be alleviated by intervening in the polarization of CD4(+) T cells remains unknown. Our research investigated the effects of intravenously administered placenta mesenchymal stromal cells (PMSCs) or treatment with extracellular EVs (EVs) derived from PMSCs (PMSC-EVs) on the polarization of CD4(+) T cells in rats with unilateral ureteral obstruction (UUO). We further verified how PMSCs affect inflammatory factor secretion and the levels of regulatory T (Treg) and Th17 CD4(+) T cells in vitro. Materials and Methods. We evaluated renal interstitial inflammation and fibrosis by pathological section staining, tested the polarization of CD4(+) T cells (Th17 and Treg phenotypes) by flow cytometry (FCM) and immunohistochemistry, and detected the cytokines secreted by CD4(+) T cells by enzyme-linked immunosorbent assay (ELISA). Results. Compared with that of control rats, the renal tissue of PMSC-treated rats exhibited lower renal Masson scores and more Foxp3(+) cell infiltration, with a significantly decreased IL17A(+)CD4(+) T cell/CD4(+) T cell ratio and a significantly elevated antiinflammatory cytokine (IL-10) level. When CD4(+) T cells were cocultured with PMSCs, CD4(+)IL17A(+) cell percentages were decreased in a UUO model after 7 days of coculture with PMSCs. The secretion of TGF-beta and IL-10 was significantly increased (P < 0.05), while the secretion of IFN-gamma, IL-17, and IL-6 was significantly decreased (P < 0.05) in the PMSC coculture group. Moreover, after treatment with PMSC-EVs, tubulointerstitial fibrosis was alleviated, and Foxp3(+)/IL-17(+) cell infiltration was increased in the kidneys of UUO model animals on day 7. Conclusions. PMSCs can convert the inflammatory environment into an anti-inflammatory environment by affecting the polarization of CD4(+) T cells and macrophages, inhibiting the inflammatory factors IFN-gamma and IL-17, and upregulating the expression of the anti-inflammatory factors TGF-beta and IL-10, ultimately leading to renal protection. Such functions may be mediated by the paracrine activity of PMSC-EVs.
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